ObsEva announced that its Phase 2 clinical trial of nolasiban (OBE001) to improve clinical pregnancy and rates of live birth in women undergoing embryo transfer after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), did not meet its primary endpoint — but increases in clinical pregnancy were seen in women treated with nolasiban relative to placebo.
The trial was particularly important for women with endometriosis who often need the treatments to conceive.
The Phase 2 IMPLANT (NCT02310802) clinical trial assessed the effectiveness and safety of a single oral administration of the oral oxytocin antagonist nolasiban in ranging doses (100 mg, 300 mg or 900 mg) to improve embryo implantation following IVF or ICSI. The trial’s primary endpoint was the percentage of women with an intra-uterine pregnancy with positive embryo heartbeat six weeks after embryo transfer.
For the study, 247 women received one of the three doses of nolasiban or a placebo four hours before a day-3 fresh embryo transfer. All women were then assessed for up to 10 weeks. Pregnancies, births, and infant health were monitored up to six months after birth.
Treatment with nolasiban increased the percentage of women with a clinical pregnancy by 9% and live birth rates by 10.4%, the results showed. For women treated with nolasiban, the live birth rates were 39.6%, while for those who received a placebo the actual live birth rates were 29.2%.
Though the clinical study did not meet its primary endpoint because a statistically significant dose-response on the percentage of women with clinical pregnancy did not occur, the results were considered clinically meaningful and parallel to a 26% increase in clinical pregnancy in women treated with nolasiban compared to placebo.
Because high progesterone levels can negatively predict live birth, the non-statistically significant dose-response could be explained — some women in the 300 mg dose group had a high progesterone level at baseline compared to the other dose groups, according to a press release.
When researchers excluded women with high levels of progesterone from the analyses, they found a statistically significant relationship between the dose of nolasiban, clinical pregnancy at week 10, and live birth rates.
In women treated with nolasiban at 900 mg, the live birth rate was 51% compared to the 30.6% rate observed in women treated with the placebo. It was the highest live birth rate seen in the study, and parallel to a 67% increase compared to placebo. The treatment was well tolerated with no safety issues reported.
“We are encouraged by the meaningful increase in pregnancy and live birth rates observed in patients treated with OBE001, particularly in women with normal progesterone levels at the time of embryo transfer,” Ernest Loumaye, MD, CEO and co-founder of ObsEva, said in the release. “We believe that if confirmed in larger trials, this would represent a major breakthrough for improving the success rate of IVF, a procedure more and more frequently used to address the need of the growing number of couples seeking treatment for infertility.”
ObsEva is now planning to initiate a Phase 3 study of nolasiban in women undergoing IVF in Europe. The trial, IMPLANT-2, should start in the first half of 2017.